中国肿瘤生物治疗杂志2026，Vol.33Issue(8)：840-847,8.DOI:10.3872/j.issn.1007-385X.2026.08.004
低氧诱导乌头酸酶2入核促进肝细胞癌PLC/PRF/5细胞的增殖和迁移
Hypoxia-induced nuclear translocation of ACO2 promotes the proliferation and migration of hepatocellular carcinoma PLC/PRF/5 cells
摘要
Abstract
Objective:To investigate the conditions and mechanisms by which hypoxia induced the nuclear translocation of aconitase 2(ACO2)and to explore the effects of ACO2 nuclear translocation on the proliferation,migration,and invasion of hepatocellular carcinoma PLC/PRF/5 cells.Methods:The expression and subcellular localization of ACO2 in human liver cancer tissues were analyzed using the Human Protein Atlas(HPA)database.The potential nuclear localization signal(NLS)of ACO2 was predicted by the NLStradamus website,and an NLS-deficient mutant gene(ACO2 Δ NLS)was constructed using genetic engineering techniques.Wild-type(ACO2WT)and mutant(ACO2ΔNLS)plasmids were transfected into human hepatocellular carcinoma PLC/PRF/5 cells,and cells in each transfection group were then cultured under either normoxic or hypoxic(1%O₂)conditions.The mechanisms underlying hypoxia-induced nuclear translocation of ACO2 were examined by immunofluorescence staining.The proliferation,migration,and invasion abilities of PLC/PRF/5 cells were assessed using EdU staining,wound healing assay,and Transwell invasion assay.The expression levels of ACO2 in nuclear and cytoplasmic fractions,as well as the levels of migration-and invasion-related proteins MMP2 and MMP9,were detected by WB.Results:HPA database analysis revealed high expression of ACO2 in both the nucleus and cytoplasm of liver cancer cells.Immunofluorescence staining and WB assay results demonstrated that hypoxia significantly induced the nuclear translocation of ACO2 in an NLS-dependent manner(all P<0.01).Functional experiments showed that hypoxia-induced nuclear translocation of ACO2 further significantly enhanced the proliferation,migration(all P<0.05),and invasion(all P<0.05)abilities of PLC/PRF/5 cells.WB analysis indicated that ACO2 nuclear translocation up-regulated the expression levels of migration-and invasion-related proteins MMP2 and MMP9(all P<0.05).Conclusion:Hypoxia could induce the nuclear translocation of ACO2 in an NLS-dependent manner,thereby promoting the proliferation,migration,and invasion abilities of PLC/PRF/5 cells.关键词
乌头酸酶2/肝细胞癌/PLC/PRF/5/低氧/增殖/迁移/侵袭Key words
aconitase 2(ACO2)/hepatocellular carcinoma(HCC)/PLC/PRF/5/hypoxia/proliferation/migration/invasion分类
医药卫生引用本文复制引用
李芸莹,李静,万源媛,何佳明,陈按,马静,王慧敏,陈地龙..低氧诱导乌头酸酶2入核促进肝细胞癌PLC/PRF/5细胞的增殖和迁移[J].中国肿瘤生物治疗杂志,2026,33(8):840-847,8.基金项目
重庆市教育委员会科学技术研究项目(KJZD-M202202701) （KJZD-M202202701）
重庆市教委"天然药物抗肿瘤"创新研究(CXQT20030) （CXQT20030）
三峡库区本土药材筛选与开发(cstc2022ycjh-bgzxm0226) （cstc2022ycjh-bgzxm0226）
重庆市科技局项目,三峡库区道地药材开发利用重庆市重点实验室开放课题重点项目(KFKT2022002) （KFKT2022002）
